Effect of chitosan based glycolipid-like nanocarrier in prevention of developing acquired drug resistance in tri-cycle treatment of breast cancer.

Multi-cycle treatment strategies were frequently applied in anti-tumor therapy in clinic. However, numerous tumors developed drug resistance during this process, and few researches paid attention to the multi-cycle treatment process when a nano carrier was adopted. In this research, a glycolipid-like nanocarrier encapsulating anti-tumor drug doxorubicin (DOX) was adopted to perform a long term drug stimulation in vitro cell line and a tri-cycle treatment on xenograft tumors to explore its effect in process of developing drug resistance. As expected, tumors treated by free doxorubicin hydrochloride (DOX·HCl) showed obvious increase of P-glycoprotein, while for tumors treated by nanocarrier encapsulated doxorubicin, the P-glycoprotein level stayed low as untreated group. Further exploration found that MDR1 gene transcription got involved in the resistance induction mechanism as its mRNA levels in DOX·HCl stimulated cells were thousands of times of those in parent cell. It concluded that tri-cycle therapy with the glycolipid-like nanocarrier would not result in acquired drug resistance. These results also implied that nano-drug delivery possessed ability in avoiding acquiring drug resistance ability during long-term treatment which may have potential use in clinic.